Disturbances of cardiac rhythm are among the most common causes of death in patients with heart disease. The drugs that are used to treat these arrhythmias are not fully understood, and in many cases, toxic. Recent promising research results from isolated tissue experiments have suggested a new approach to the use of combinations of agents, based on their frequency and voltage dependent actions. This project will evaluate frequency-dependent actions of one of the major groups of antiarrhythmic agents on cardiac conduction and arrhythmia behaviour in intact animals. The actions of antiarrhythmic drugs in-vivo will be correlated with results obtained in-vitro and predicted by the modulated receptor hypothesis. The experiments will: 1. Examine and contrast use-dependent effects of lidocaine, mexiletine and quinidine on conduction in-vivo. 2. Determine if in-vivo differences in use-dependent behavior by lidocaine, mexiletine and quinidine conform to the modulated receptor hypothesis. 3. Determine if drugs that selectively prolong the QT interval (inactivated state) will enhance rate-related conduction slowing more by mexiletine and lidocaine than by quinidine. 4. Determine if drugs that prolong the QT interval will selectively enhance the efficacy of lidocaine and mexiletine more than that of quinidine in suppressing a post-infarct arrhythmia. Ultimately, information will be used to determine optimal conditions for a favorable electrophysiologic and antiarrhythmic actions by antiarrhythmic drug combinations.